Over the last 6 years, the Office of Chief Medical Examiner (OCM E), Western District, has documented a three fold increase in prescription drug related mortality in Southwestern Virginia. The opioid drugs oxycodone, methadone, and fentanyl were identified as the direct or contributing cause of death. In 2002, drug deaths where methadone was a direct or contributing cause of death occurred at a rate of 5.76/1000, 000 population in our region, greater than the rates of metropolitan Philadelphia and Oklahoma. Within the state of Virginia in 2001, 40 of the 100 deaths from oxycodone were in the southwestern OCME region; in 2002 twenty-six of the 89 of oxycodone deaths were from our region. The aims of the research are as follows: I. Compare deaths where opioids are a direct/contributing cause of death to: (a) drug deaths where opioids are not identified, and (b) the general medical examiner population. II. Compare deaths with differing opioids as a direct/contributing cause of death. III. Provide detailed description of prescription drug concentrations in post-mortem fluid and tissue concentrations, specifically opioids and benzodiazepines. The study design is a retrospective population based record review. The proposed research is significant because it will characterize deaths that occur in a population that is often difficult to evaluate secondary to the lifestyle associated with drug use and abuse. In addition, the data has been procured and is available for analysis. Finally, the proposed research will shed more light on those who are using and abusing prescription drugs and are at risk for overdose. The long term goal of this proposed research is to characterize a population of deaths in rural southwest Virginia that are the result of misuse and abuse of prescription opioid medications and characterize their lethality in combination with other psychoactive substances. Dissemination of this information will aid clinicians in identifying a group of prescription drug abusers at risk for death and provide better knowledge of reference ranges for fatal opioid toxicity.